c-Myc in breast cancer.

Abstract

Ever since Bishop and his co-workers discovered the c-myc gene in the late 1970s (Bishop 1982), voluminous literature has documented its central role in proliferation and malignant transformation of human and animal cells (Amati et al. 1998, Bouchard et al. 1998, Dang et al. 1999). Most, if not all, types of human malignancy have been reported to have amplification and/or overexpression of this gene, although the frequency of these alterations varies greatly among different reports (Nesbit et al. 1999). In 1992, researchers started to realize that aberrant expression of c-myc could cause apoptosis (Evan et al. 1992, Shi et al. 1992), although the phenomenon had actually been observed much earlier (Wurm et al. 1986). Studies in recent years have further shown that the c-myc gene regulates growth, both in the sense of cell size and in the context of tissue differentiation (Gandarillas & Watt 1997, Iritani & Eisenman 1999, Johnston et al. 1999, Schmidt 1999, Schuhmacher et al. 1999). Thus, it is now known that the c-myc gene participates in most aspects of cellular function, including replication, growth, metabolism, differentiation, and apoptosis (Packham & Cleveland 1995, Hoffman & Liebermann 1998, Dang 1999, Dang et al. 1999, Elend & Eilers 1999, Prendergast 1999). How the c-Myc protein may be specifically directed to perform one, but not the others, of these functions is still obscure, despite the fact that the relevant literature has been accumulating at a fast pace in the past two decades. This review focuses on the profound roles of c-Myc in breast cancer and in the actions of the hormones that are eitologically related to breast cancer.

C‐myc gene expression alone is sufficient to confer resistance to antiestrogen in human breast cancer cells

“…The estrogen independence or antiestrogen resistance phenotype achieved during human breast cancer progression may due in large parts to the acquisition of elevated c-myc expression via c-myc gene amplification or enhanced, deregulated c-myc gene transcription. Indeed, a number of studies 6 have demonstrated a positive correlation between c-myc gene amplification and ER negativity (indicative of estrogenindependent proliferation) in human breast tumors. Therefore, the status of c-myc expression may be a useful predictive marker for hormonal therapy, especially with respect to the development of antiestrogen resistance, of breast cancer in women.…”

“…4 In human breast carcinomas, genetic abnormalities including c-myc amplification, rearrangement and overexpression have been widely reported. 5,6 A meta-analysis of 29 studies has revealed that, on average, 15.5% of breast cancer biopsies demonstrate c-myc gene amplification of 3-fold or greater. 6,7 Many, but not all, studies have found that c-myc amplification is significantly associated with tumour grade, lymph-node metastasis, negative estrogen and progesterone receptor status, risk of relapse, high S-phase fraction and amplification of c-erbB-2.…”

“…5,6 A meta-analysis of 29 studies has revealed that, on average, 15.5% of breast cancer biopsies demonstrate c-myc gene amplification of 3-fold or greater. 6,7 Many, but not all, studies have found that c-myc amplification is significantly associated with tumour grade, lymph-node metastasis, negative estrogen and progesterone receptor status, risk of relapse, high S-phase fraction and amplification of c-erbB-2. 6 Using real-time RT-PCR, Bieche et al 8 reported that c-myc is over expressed in 22% of breast tumors (n ϭ 134), with levels 3.2-to 19-times that of normal breast tissue.…”

“…6,7 Many, but not all, studies have found that c-myc amplification is significantly associated with tumour grade, lymph-node metastasis, negative estrogen and progesterone receptor status, risk of relapse, high S-phase fraction and amplification of c-erbB-2. 6 Using real-time RT-PCR, Bieche et al 8 reported that c-myc is over expressed in 22% of breast tumors (n ϭ 134), with levels 3.2-to 19-times that of normal breast tissue. It has also been reported that BRCA1, a breast cancer susceptibility gene, may function as a tumour suppressor by regulating c-myc, providing a molecular explanation for some of the effects of the BRCA1 gene product.…”

BRCA1 gene in breast cancer

“…c-Myc is a protooncogene that functions in diverse cellular processes, including cell proliferation, development, apoptosis, and cellular transformation (reviewed in Nass and Dickson, 1997;Liao and Dickson, 2000). Through its two DNAbinding domains (Myc box 1 and Myc box 2), c-Myc can either stimulate or repress transcription.…”